S Arena1,2, M Salati3, G Sorgentoni4, F Barbisan5, M Orciani6. 1. Department of Oncology, University of Torino, SP 142, Km 3.95, 10060, Candiolo, TO, Italy. 2. Candiolo Cancer Institute-FPO, IRCCS, Candiolo, TO, Italy. 3. Unit of Thoracic Surgery, AOU Ospedali Riuniti, via Tronto 10/a, 60126, Ancona, Italy. 4. Department of Molecular and Clinical Sciences-Histology, Università Politecnica delle Marche, via Tronto 10/a, 60020, Ancona, Italy. 5. Unit of Pathology, AOU Ospedali Riuniti, via Tronto 10/a, 60126, Ancona, Italy. 6. Department of Molecular and Clinical Sciences-Histology, Università Politecnica delle Marche, via Tronto 10/a, 60020, Ancona, Italy. m.orciani@univpm.it.
Abstract
PURPOSE: The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence. METHODS: MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion. RESULTS: C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (α-SMA, HI-1α, MMP11, VEGF, CXCL12, TGF-β1, TGF-βRII, IL6, TNFα) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs. CONCLUSIONS: MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.
PURPOSE: The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence. METHODS: MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion. RESULTS: C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (α-SMA, HI-1α, MMP11, VEGF, CXCL12, TGF-β1, TGF-βRII, IL6, TNFα) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs. CONCLUSIONS: MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.
Authors: M Orciani; G Sorgentoni; M Torresetti; Roberto Di Primio; G Di Benedetto Journal: Breast Cancer Res Treat Date: 2016-03-08 Impact factor: 4.872
Authors: Eunice Yuen Ting Lau; Jessica Lo; Bowie Yik Ling Cheng; Mark Kin Fai Ma; Joyce Man Fong Lee; Johnson Kai Yu Ng; Stella Chai; Chi Ho Lin; Suk Ying Tsang; Stephanie Ma; Irene Oi Lin Ng; Terence Kin Wah Lee Journal: Cell Rep Date: 2016-04-28 Impact factor: 9.423
Authors: D Weekes; T G Kashima; C Zandueta; N Perurena; D P Thomas; A Sunters; C Vuillier; A Bozec; E El-Emir; I Miletich; A Patiño-Garcia; F Lecanda; A E Grigoriadis Journal: Oncogene Date: 2015-09-21 Impact factor: 9.867